1. Technical Field
The present invention is related to immunology. More particularly, the present invention is related to producing improved immune response to an antigen by targeting the antigen to the immune system.
2. State of the Art
Immunogenicity of antigens in vivo or their potency in vitro is dependent on several factors. Important among such factors are the characteristics of the antigen itself and of the host. Molecular properties of the antigen itself might include: (a) size of the antigen, correlated with the number of antigenic determinants; (b) affinity for functional structures of cells in the immune system, such as immunoglobulins on B cells, cell surface membranes of antigen-presenting cells, Ia molecules after being processed, or T cell receptors with Ia molecules; or (c) susceptibility or resistance to lysosomal enzymes. In the whole animal, the distribution, catabolism, and excretion of the injected antigen also influence the magnitude of immune response. Of course, the route of administration, use of adjuvants, and antigen dosage are some other factors which influence the fate of antigen and the immune response.
Despite rapid advances in immunology, a problem in inducing protective immunization or producing an effective vaccine is faced when the antigens are either too weak or too limited in quantity to be used as immunogens. The present invention now overcomes this limitation in immunology and provides a means of achieving enhanced immune response to an antigen by targeting the antigen to the immune system thereby inducing improved antigenic potency for an otherwise weaker entity.
Several studies have shown that B cells can function as antigen-presenting cells. These fall into three categories. First, at relatively high antigen concentration, B cells and B cell tumors have been shown to take up antigen nonspecifically and to present it to T cells (Chesnut, et al. J. Immunol. 128:1764, 1982). For small resting B cells, this function is much more radiosensitive than for accessory cells (AC); such as, dendritic cells [Steinman, et al. J. Exp. Med. 149:1, 1979] or macrophages) (Ashwell, et al. J. Exp. Med. 159:881, 1984). Second, antigen-specific B cells have shown to take up antigen efficiently at low concentration via their specific surface immunoglobulin and to stimulate specific T cells (Rock, et al. J. Exp. Med. 160:1102, 1984; Malynn, et al. J. Immunol. 132:2253, 1984). This mechanism is probably the most physiological type of B cell presentation, but it is difficult to purify antigen-specific B cells experimentally. Third, advantage has been taken of using xenogeneic anti-immunoglobulin antibodies as an antigen (Chesnut, et al. J. Immunol. 126:1075, 1981; Tony, et al. J. Exp. Med. 161:223, 1985). These antibodies can bind to all B cells, but bind with high affinity as in the second approach, and so are presented more effectively than the corresponding xenogeneic immunoglobulin not specific for B cell surface Ig. Thus, this third approach combines some of the advantages of each of the other two approaches; however, so far this approach has been useful only for stimulating T cells specific for xenogeneic immunoglobulin. The present invention now makes it possible to direct any antigen towards the immune system and determine its effect on immunogenicity.